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Role of hydrogen sulfide (H2S) in the inflammatory and nociceptive responses induced by carrageenan in the rat temporomandibular joint

Grant number: 14/24518-1
Support Opportunities:Regular Research Grants
Duration: April 01, 2015 - June 30, 2017
Field of knowledge:Health Sciences - Dentistry - Oral and Maxillofacial Surgery
Principal Investigator:Marcelo Nicolas Muscara
Grantee:Marcelo Nicolas Muscara
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated researchers:Soraia Katia Pereira Costa


Over the last decade, the endogenous production of hydrogen sulfide (H2S), a well known environmental pollutant, has been characterized in mammals, as well as its participation in several organic functions, such as vascular reactivity, mitochondrial activity and inflammatory response. Regarding the latter aspect, and despite some divergences that appear in the literature concerning the pro-or anti-inflammatory effects of H2S, more recent studies demonstrate that the addition of a chemical moiety capable of releasing H2S to the structure of traditional NSAIDs results in compounds that present with lower gastric toxicity and adverse cardiovascular effects in relation to the original non-steroidal anti-inflammatory drugs (NSAIDs), without any loss of their anti-inflammatory action.Our group has demonstrated that treatment of rats with the Lawesson's reagent (an H2S-releasing agent) results in significant reduction of both joint swelling and hyperalgesia secondary to the knee joint arthritis / synovitis induced by the intra-articular injection of carrageenan (CGN). Similarly, other researchers have shown the beneficial effects of H2S donors in other models of knee joint arthritis, such as those induced by kaolin / CGN or Freund's adjuvant. More recently, we demonstrated that the presence of a H2S-releasing moiety in the naproxen molecule, which results in the compound ATB-346, not only does not interfere with the anti-inflammatory activity of the NSAID naproxen in the carrageenan-induced knee joint synovitis in rats, but also avoids the unwanted gastric effects of the latter. However, there are no reports in the literature on the effects of the administration of H2S donors in the temporomandibular joint (TMJ) arthritis.Temporomandibular disorders (TMDs) are a group of diseases associated with the TMJ, masticatory muscles and/or other facial structures. Approximately 50% of the population exhibits some sign of TMDs, and around 10 to 20% of these patients present with severe symptoms, and the consequent drop in quality of life. TMJ arthritis is probably the most important of the TMDs, and the symptoms are partially controlled by the use of NSAIDs and/or low dose glucocorticoids.Given the need for therapeutic alternatives to control these diseases (considering the limitations imposed by the adverse side effects of NSAIDs and corticosteroids), this study aims to assess the effect of H2S donors in a rat model of CGN-induced TMJ arthritis/synovitis, the participation of endogenous H2S in the etiology of the disease and the mechanisms involved. (AU)

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Scientific publications (5)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
COAVOY-SANCHEZ, SILVIA A.; COSTA, SORAIA K. P.; MUSCARA, MARCELO N.. Hydrogen sulfide and dermatological diseases. British Journal of Pharmacology, v. 177, n. 4, SI, p. 857-865, . (17/16409-6, 14/24518-1, 16/06146-5)
COAVOY-SANCHEZ, SILVIA ABIGAIL; CERQUEIRA, ANDERSON ROMERIO AZEVEDO; TEIXEIRA, SIMONE APARECIDA; SANTAGADA, VINCENZO; ANDREOZZI, GIORGIA; CORVINO, ANGELA; SCOGNAMIGLIO, ANTONIA; SPARACO, ROSA; CALIENDO, GIUSEPPE; SEVERINO, BEATRICE; et al. Beneficial Effects of Two Hydrogen Sulfide (H2S)-Releasing Derivatives of Dexamethasone with Antioxidant Activity on Atopic Dermatitis in Mice. PHARMACEUTICS, v. 15, n. 7, p. 19-pg., . (13/04151-3, 14/24518-1, 17/16409-6, 19/14051-2)
DOS SANTOS, JAQUELINE ROCHA BORGES; RAE, MARIANA; TEIXEIRA, SIMONE APARECIDA; MUSCARA, MARCELO NICOLAS; SZUMLINSKI, KAREN K.; CAMARINI, ROSANA. The effect of MK-801 on stress-ethanol cross-sensitization is dissociable from its effects on nNOS activity. ALCOHOL, v. 112, p. 9-pg., . (14/24518-1)
COAVOY-SANCHEZ, SILVIA ABIGAIL; MARQUES, LEONARDO ANDRE DA COSTA; COSTA, SORAIA KATIA PEREIRA; MUSCARA, MARCELO NICOLAS. Role of Gasotransmitters in Inflammatory Edema. Antioxidants & Redox Signaling, v. N/A, p. 20-pg., . (13/04151-3, 14/24518-1, 17/16409-6, 19/14051-2)
CAMPOS, DAIANA; RAVAGNANI, FELIPE G.; GURGUEIRA, SONIA A.; VERCESI, ANIBAL E.; TEIXEIRA, SIMONE A.; COSTA, SORAIA K. P.; MUSCARA, MARCELO N.; FERREIRA, HELOISA H. A.. Increased glutathione levels contribute to the beneficial effects of hydrogen sulfide and inducible nitric oxide inhibition in allergic lung inflammation. International Immunopharmacology, v. 39, p. 57-62, . (14/24518-1, 12/02145-3, 13/04151-3)

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